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Array-Based Pathology Model

 

Apoptosis Related Model

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An Example of Pathology-Model Based Target Validation
Background: An in vitro study had suggested that molecule X secreted by tumor cells might induce T cell apoptosis, so as to help tumor cells escape from T cell mediated tumor cell killing. The purpose of the profiling project was to find evidence supporting this suggestion and to evaluate suitability of the molecule as a target for antibody therapeutics.
Procedures Results Picture
Antibody production Specific antibody was produced. The antibody recognized a single band with correct molecular weight in Western blot (as indicated by the arrow).
IHC tissue profiling was performed in standard normal tissue arrays. IHC tissue profiling showed a dominant cytoplasmic staining pattern of the molecule in a wide range of organs of the human body.
IHC tissue profiling was performed in standard tumor tissue arrays. IHC tissue profiling showed slightly higher than normal expression levels of the molecule in a wide range of tumors.
IHC (left) and TUNEL (right) analyses to correlate apoptic index with expression levels of the molecule in our apoptosis related model. High expression level of the molecule (left top brown staining indicated by the arrow) did not correlate with the apoptotic index in the model. The brown dots on the right indicated by arrows are apoptotic bodies.
IHC detection of CD4 and CD8 populations in the apoptosis model. There were abundant CD4 and CD8 lymphocytes (indicated by arrows) near or within the tumor cells that showed high level of molecule X.
Pharmacological aspect IHC showed high expression levels of the molecule in many vital organs. The arrows indicate strong staining in the tubular epithelial cells of the kidney.
Conclusion Our pathology model-based analyses did not support the original hypothesis that molecule X might induce T cell apoptosis. The high expression levels of the molecule found in many vital organs indicate that the molecule is not suitable as a target for antibody therapeutics.
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